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365: Different GVHD Clinical Profile among Patients who Received Cord Blood, Compared to those who Received Marrow or Peripheral Blood
134
Poster Session II
365
366
DIFFERENT GVHD CLINICAL PROFILE AMONG PATIENTS WHO RECEIVED CORD BLOOD, COMPARED TO THOSE WHO RECEIVED MARROW OR PERIPHERAL BLOOD Funke, V.A.M., Nunes, E.C., Medeiros, L., Setubal, D.C., Ruiz, J., Oliveira, M.M., Bittencourt, M.A., Bonfim, C., Neto, J.Z., Medeiros, C.R., Pasquini, R. Hospital de Clınicas - Federal University of Parana, Curitiba, Parana, Brazil.
ALLOSPECIFIC EFFECTOR MEMORY T CELLS HAVE DECREASED ABILITY TO INDUCE ACUTE GVHD Chen, B.J., Wu, J., DeOliveira, D., Chao, N.J. Duke University Medical Center, Durham, NC.
It is well known that transplants from cord blood stem cells have lower incidence of graft-versus-host disease, which allows procedures with more HLA disparities when compared to marrow. The objective of this study, however is to determine if there is a different clinical expression of GVHD beteween receptors of peripheral blood/marrow versus cord blood. Patients and Methods: From October 1979 to June 2007, 1530 patients were transplanted at the BMT center of the Federal University of Parana. We retrieved the database of our institution and divided the patients into two categories. Group one: 1390 patients who received bm or pb as stem cell source. Group 2: 140 patients who received cord blood. Main differences between the two goups are listed at the table below. Statystical Analysis: Kaplan Meier was used for survival and Fisher test for comparison of categoric variables. Results: See table 1. Conclusions: 1. There was a lower incidence of lung and oral involvement by chronic GVHD and a higher incidence of gut involvement on patients who received CB as compared to PB and Marrow. Furthermore, we did not see any case of bronchiolitis obliterans in the CB group. 2. There was less oral and more gut and liver involvement by acute GVHD in the CB group. 3. Overall incidence of chronic GVHD was lower for the cord blood group. There were a higher frequency of acute GVHD grade II-IV among CB recipients, possibly because of the increased frequency of HLA disparity.
CB Marrow/PB: acute and chronic GVHD Characteristics
Group 1 (CB) Group2 (BM/PB) P value
N 140 1390 Age (M) years 6 20 SCT donor 0.0001 related 18 1235 unrelated 122 155 HLA 0.0001 compatible 34 1296 1 mismatch (A, B, DR) 47 89 other 59 5 Male/Female 83/57 841/549 40 (29%) 289 (21%) Sex mismatch (male recipient/female donor) A-GVHD 51 (36%) 350 (45%) 0.0385 Grade III-IV 26/51 (51%) 113/350 (32%) Skin 41 (80%) 297 (85%) Liver 12 (24%) 141 (40%) 0.0212 Oral 2 (4%) 31 (8%) Lung 0 4 (1%) Gut 20 (15%) 89 (25%) 0.0440 C-GVHD extensive 13/95 av (14%) 238/1115 av (21%) severe 4/13 (30%) 95/238 (40%) C-GVHD organ Skin 7 (53%) 106 (45%) Liver 10 (77%) 92 (39%) 0.0084 Oral 2 (15%) 108 (45%) 0.0434 Lung 1 *(7%) 36 (15%) Gut 6 (46%) 48 (20%) 0.0376 Survival (%) 68 (49%) 721 (52%) Survival (M) days 196 (0–5231) 1028 (0–9078)
*BOOP.
Several different groups have independently demonstrated that non-allospecific memory T cells do not induce GVHD. The data related to the ability of allospecific memory T cells to induce GVHD have not been conclusive. In order to study this question more definitely, we have developed a novel GVHD model using TEa TCR transgenic mice as donors. TEa CD41 TCR transgenic mice (C57BL/6 background) express a TCR that recognizes the peptide ASFEAQGLANIAVDKA in the context of I-Ab. This peptide corresponds to positions 52–68 from the alpha-chain of I-E class II molecules and is expressed in all APCs from H-2b/I-E1 strains such as CB6F1 mice. Titration experiment demonstrated that as few as 1 105 TEa cells were able to induce lethal GVHD in lethally irradiated CB6F1 recipients, making it an ideal model to study the ability of allospecific memory T cells to induce GVHD. Because sufficient numbers of allospecific memory phenotype T cells could not be obtained from the TEa mice or C57BL/6 CD45.1 mice containing TEa cells after priming, we chose the Rag1-/- model. TEa cells were first parked in Rag1-/- mice and then were immunized with irradiated CB6F1 cells. Eight weeks later, TEa cells were harvested from the spleens and effector memory T cells were obtained after depletion of CD62L1 cells. Many TEa cells that were parked in the Rag1-/- mice but were not immunized with alloantigens also obtained the effector memory T cell phenotype. These cells were termed as ‘‘unprimed TEM’’ while those from primed animals were termed as ‘‘primed TEM’’. Both primed and unprimed effector memory TEa cells were able to respond to alloantigens in vitro. However, neither primed nor unprimed effector memory TEa cells was able to induce lethal GVHD in vivo and all animals in the effector memory T cell groups survived more than 100 days post transplantation. In contrast, all naive T cell recipients developed lethal GVHD and died within 35 days after transplantation. These data demonstrate that, similar to non-allospecific memory T cells, allospecific effector memory T cells also have decreased ability to induce GVHD when compared with naive T cells. This is an excellent model for us to study the unique immune response mediated by allospecific memory T cells in GVHD.
367 SURVIVAL AFTER EXTRACORPOREAL PHOTOPHERESIS (ECP) FOR TREATMENT OF GRAFT-VERSUS-HOST DISEASE (GVHD) IS PREDICTED BY GVHD CLASSIFICATION AS PROPOSED BY NATIONAL INSTITUTE OF HEALTH (NIH) CONSENSUS CRITERIA Jagasia, M.1, Stricklin, G.2, Logue, M.1, Lucid, C.1, Fife, H.1, Mitchell, J.1, Chen, H.3, Hunt, C.1, Kassim, A.1. 1 Vanderbilt University Medical Center, Nashville, TN; 2 Vanderbilt University Medical Center, Nashville, TN; 3 Vanderbilt University Medical Center, Nashville, TN. ECP is used in GVHD treatment with variable response. The clinical phenotype of GVHD associated with ECP responsiveness is not clear. Subtypes of GVHD proposed by NIH consensus criteria affect survival after allogeneic stem cell transplant (SCT) (BBMT 2007 Oct; 13(10):1207–15). We hypothesized that survival after ECP will be determined by NIH subtypes of GVHD. Methods: Review of patients undergoing ECP for GVHD treatment was done. 55 patients (pts.) were identified and GVHD was reclassified using NIH criteria. Pts. with acute GVHD (aGVHD) were graded using Glucksberg criteria. Pts. with overlap or classic chronic GVHD (cGVHD) were scored using NIH criteria. Overall survival (OS) was measured from starting ECP. ECP indication was steroid dependency or refractoriness. Results: Classic aGVHD (26%), recurrent aGVHD (7%), overlap cGVHD (16%) and classic cGVHD (51%) accounted for the subtypes. Pts. started ECP at a median of 216 days after SCT (range, 41 to 2946). The median number of GVHD recurrences prior to ECP start was 2 (range, 0–6). Pts. with classic cGVHD started ECP significantly later (145 days vs. 53 days, P \ 0.001), continued it for a longer time
Poster Session II
365
366
DIFFERENT GVHD CLINICAL PROFILE AMONG PATIENTS WHO RECEIVED CORD BLOOD, COMPARED TO THOSE WHO RECEIVED MARROW OR PERIPHERAL BLOOD Funke, V.A.M., Nunes, E.C., Medeiros, L., Setubal, D.C., Ruiz, J., Oliveira, M.M., Bittencourt, M.A., Bonfim, C., Neto, J.Z., Medeiros, C.R., Pasquini, R. Hospital de Clınicas - Federal University of Parana, Curitiba, Parana, Brazil.
ALLOSPECIFIC EFFECTOR MEMORY T CELLS HAVE DECREASED ABILITY TO INDUCE ACUTE GVHD Chen, B.J., Wu, J., DeOliveira, D., Chao, N.J. Duke University Medical Center, Durham, NC.
It is well known that transplants from cord blood stem cells have lower incidence of graft-versus-host disease, which allows procedures with more HLA disparities when compared to marrow. The objective of this study, however is to determine if there is a different clinical expression of GVHD beteween receptors of peripheral blood/marrow versus cord blood. Patients and Methods: From October 1979 to June 2007, 1530 patients were transplanted at the BMT center of the Federal University of Parana. We retrieved the database of our institution and divided the patients into two categories. Group one: 1390 patients who received bm or pb as stem cell source. Group 2: 140 patients who received cord blood. Main differences between the two goups are listed at the table below. Statystical Analysis: Kaplan Meier was used for survival and Fisher test for comparison of categoric variables. Results: See table 1. Conclusions: 1. There was a lower incidence of lung and oral involvement by chronic GVHD and a higher incidence of gut involvement on patients who received CB as compared to PB and Marrow. Furthermore, we did not see any case of bronchiolitis obliterans in the CB group. 2. There was less oral and more gut and liver involvement by acute GVHD in the CB group. 3. Overall incidence of chronic GVHD was lower for the cord blood group. There were a higher frequency of acute GVHD grade II-IV among CB recipients, possibly because of the increased frequency of HLA disparity.
CB Marrow/PB: acute and chronic GVHD Characteristics
Group 1 (CB) Group2 (BM/PB) P value
N 140 1390 Age (M) years 6 20 SCT donor 0.0001 related 18 1235 unrelated 122 155 HLA 0.0001 compatible 34 1296 1 mismatch (A, B, DR) 47 89 other 59 5 Male/Female 83/57 841/549 40 (29%) 289 (21%) Sex mismatch (male recipient/female donor) A-GVHD 51 (36%) 350 (45%) 0.0385 Grade III-IV 26/51 (51%) 113/350 (32%) Skin 41 (80%) 297 (85%) Liver 12 (24%) 141 (40%) 0.0212 Oral 2 (4%) 31 (8%) Lung 0 4 (1%) Gut 20 (15%) 89 (25%) 0.0440 C-GVHD extensive 13/95 av (14%) 238/1115 av (21%) severe 4/13 (30%) 95/238 (40%) C-GVHD organ Skin 7 (53%) 106 (45%) Liver 10 (77%) 92 (39%) 0.0084 Oral 2 (15%) 108 (45%) 0.0434 Lung 1 *(7%) 36 (15%) Gut 6 (46%) 48 (20%) 0.0376 Survival (%) 68 (49%) 721 (52%) Survival (M) days 196 (0–5231) 1028 (0–9078)
*BOOP.
Several different groups have independently demonstrated that non-allospecific memory T cells do not induce GVHD. The data related to the ability of allospecific memory T cells to induce GVHD have not been conclusive. In order to study this question more definitely, we have developed a novel GVHD model using TEa TCR transgenic mice as donors. TEa CD41 TCR transgenic mice (C57BL/6 background) express a TCR that recognizes the peptide ASFEAQGLANIAVDKA in the context of I-Ab. This peptide corresponds to positions 52–68 from the alpha-chain of I-E class II molecules and is expressed in all APCs from H-2b/I-E1 strains such as CB6F1 mice. Titration experiment demonstrated that as few as 1 105 TEa cells were able to induce lethal GVHD in lethally irradiated CB6F1 recipients, making it an ideal model to study the ability of allospecific memory T cells to induce GVHD. Because sufficient numbers of allospecific memory phenotype T cells could not be obtained from the TEa mice or C57BL/6 CD45.1 mice containing TEa cells after priming, we chose the Rag1-/- model. TEa cells were first parked in Rag1-/- mice and then were immunized with irradiated CB6F1 cells. Eight weeks later, TEa cells were harvested from the spleens and effector memory T cells were obtained after depletion of CD62L1 cells. Many TEa cells that were parked in the Rag1-/- mice but were not immunized with alloantigens also obtained the effector memory T cell phenotype. These cells were termed as ‘‘unprimed TEM’’ while those from primed animals were termed as ‘‘primed TEM’’. Both primed and unprimed effector memory TEa cells were able to respond to alloantigens in vitro. However, neither primed nor unprimed effector memory TEa cells was able to induce lethal GVHD in vivo and all animals in the effector memory T cell groups survived more than 100 days post transplantation. In contrast, all naive T cell recipients developed lethal GVHD and died within 35 days after transplantation. These data demonstrate that, similar to non-allospecific memory T cells, allospecific effector memory T cells also have decreased ability to induce GVHD when compared with naive T cells. This is an excellent model for us to study the unique immune response mediated by allospecific memory T cells in GVHD.
367 SURVIVAL AFTER EXTRACORPOREAL PHOTOPHERESIS (ECP) FOR TREATMENT OF GRAFT-VERSUS-HOST DISEASE (GVHD) IS PREDICTED BY GVHD CLASSIFICATION AS PROPOSED BY NATIONAL INSTITUTE OF HEALTH (NIH) CONSENSUS CRITERIA Jagasia, M.1, Stricklin, G.2, Logue, M.1, Lucid, C.1, Fife, H.1, Mitchell, J.1, Chen, H.3, Hunt, C.1, Kassim, A.1. 1 Vanderbilt University Medical Center, Nashville, TN; 2 Vanderbilt University Medical Center, Nashville, TN; 3 Vanderbilt University Medical Center, Nashville, TN. ECP is used in GVHD treatment with variable response. The clinical phenotype of GVHD associated with ECP responsiveness is not clear. Subtypes of GVHD proposed by NIH consensus criteria affect survival after allogeneic stem cell transplant (SCT) (BBMT 2007 Oct; 13(10):1207–15). We hypothesized that survival after ECP will be determined by NIH subtypes of GVHD. Methods: Review of patients undergoing ECP for GVHD treatment was done. 55 patients (pts.) were identified and GVHD was reclassified using NIH criteria. Pts. with acute GVHD (aGVHD) were graded using Glucksberg criteria. Pts. with overlap or classic chronic GVHD (cGVHD) were scored using NIH criteria. Overall survival (OS) was measured from starting ECP. ECP indication was steroid dependency or refractoriness. Results: Classic aGVHD (26%), recurrent aGVHD (7%), overlap cGVHD (16%) and classic cGVHD (51%) accounted for the subtypes. Pts. started ECP at a median of 216 days after SCT (range, 41 to 2946). The median number of GVHD recurrences prior to ECP start was 2 (range, 0–6). Pts. with classic cGVHD started ECP significantly later (145 days vs. 53 days, P \ 0.001), continued it for a longer time